Table 1.
Expression of NOD1 and NOD2 in chronic inflammatory disorders
| Category | Disorder | Cells/Tissues studied | NLR | NLR expression | Refs |
|---|---|---|---|---|---|
| Inflammatory bowel disease | Ulcerative colitis | Lower colonic mucosal biopsies from healthy and UC patients with severe/mild inflammation or are in remission. | NOD1 | Eightfold increase in severe UC patients relative to mild/healthy samples. Remission patients had similar expression levels to healthy individual. | 34 |
| Crohn's disease | Paneth cells from ileal crypts of CD patients. | NOD2 | Increased in ileal crypts. No increase in colonic crypts. | 41 | |
| Autoimmune disease | Blau syndrome | BMDMs from WT or NOD2 R314Q knock‐in mice. | NOD2 | Stimulation with poly(I:C) increased NOD2 expression in WT but not NOD2 R314Q knock‐in cells. | 67 |
| Rheumatoid arthritis | Synovial macrophages and fibroblasts from synovium of RA patients. | NOD2 | Increased expression in the synovium of RA patients. | 68 | |
| Synovial tissue from RA patients. | NOD1 | Increased expression in lining and sublining of RA synovial tissue. | 69 | ||
| Peripheral blood mononuclear cells (PBMCs) and synovial fluid T cells (SFTCs) from RA patients. | NOD1 | No increase in expression in PBMCs or SFTCs. | 70 | ||
| NOD2 | Significantly increased expression in PBMCs and SFTCs. | ||||
| Allergic reaction | Allergic rhinitis | Human nasal epithelial cells (HNECs) isolated from nasal mucosa biopsies of AR patients in/out of pollen season. | NOD1 | Reduced expression in HNECs from pollen season AR sufferers, relative to AR sufferers outside pollen season. | 71 |
| NOD2 | Expression uniform between AR sufferers and healthy controls regardless of pollen season | ||||
| Nasal mucosal biopsies from AR patients. | NOD1 | Increased in AR patients relative to healthy individuals. | 72 | ||
| NOD2 | Increased in AR patients relative to healthy individuals. | ||||
| Cardiovascular disease | Atherosclerosis | Serum from Apoe−/− and Apoe−/− Nod1−/− mice. | NOD1 | Required for atherosclerotic lesions development. | 76 |
| Endothelial cells and macrophages from human carotid plaques and healthy arteries. | NOD2 | Fourfold expression increase in plaques relative to healthy mammary arteries. Barely detectable in healthy arteries. | 77 | ||
| Behçet disease | Bronchoalveolar lavage (BAL) from BD patients and healthy controls. | NOD2 | Increased significantly in BD patients relative to healthy controls | 74 | |
| Metabolic disease | Metabolic syndrome | Abdominal subcutaneous adipose tissue and adipocytes from MetS patients and healthy controls. | NOD1 | Increased expression in MetS adipose tissue and adipocytes. | 80 |
| NOD2 | No significant expression difference between MetS and healthy controls. | ||||
| Gestational diabetes | Subcutaneous and omental adipose tissue from GDM and normal glucose tolerance (NGT) women. | NOD1 | Expression significantly higher in GDM women relative to NGT women. | 81 |
Abbreviations: AR, allergic rhinitis; BD, Behçet's disease; BMDM, bone‐marrow‐derived macrophages; CD, Crohn's disesae; GDM, gestational diabetes mellitus; HNEC, human nasal epithelial cells; IEC, intraepithelial cells; NGT, normal glucose tolerance; NLR, NOD‐like receptor; NOD1, nucleotide‐binding oligomerization domain 1; PBMC, peripheral blood mononuclear cells; RA, rheumatoid arthritis; SFTC, synovial fluid T cells; UC, ulcerative colitis; WT, wild‐type.
Listed in this table are studies that have made direct links between chronic inflammatory disorders and increased NOD1/NOD2 expression and their findings. Disorders associated with NOD1/NOD2 include inflammatory bowel disease, autoimmune disease, allergic reactions, cardiovascular disease and metabolic diseases.